An essential role for CCAAT/enhancer binding protein β in bleomycin-induced pulmonary fibrosis


  • No conflicts of interest were declared.


Pulmonary fibrosis is characterized by inflammation, genesis of myofibroblasts, and abnormal tissue repair. Despite extensive research, its pathogenesis remains incompletely understood. Previously, the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) was found to be a key regulator of myofibroblast differentiation in vitro, and to be involved in the acute phase and inflammatory responses. In an attempt to test the role of C/EBPβ in the development of pulmonary fibrosis, experiments using C/EBPβ null mice and their wild-type littermates were conducted. Our findings indicated that, compared to wild-type mice, animals deficient in C/EBPβ showed significantly reduced fibrotic lesions and collagen deposition in the lung upon endotracheal injection of bleomycin. Further studies on the mechanisms by which C/EBPβ regulates fibrosis indicated that knockout of C/EBPβ attenuates inflammatory cytokine expression in bleomycin-treated mice. The reduced α-smooth muscle actin gene expression in either isolated lung fibroblasts or lung tissue from bleomycin or saline-treated C/EBPβ deficient mice suggests that C/EBPβ regulates myofibroblast differentiation during fibrosis. Consistent with this finding, cells from C/EBPβ deficient mice exhibited higher proliferative rates than those from wild-type mice. These data suggest that C/EBPβ plays an essential role in pulmonary fibrosis and that this role appears to be multifactorial with respect to cytokine expression, cell differentiation, and proliferation. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.